Hindawi Publishing Corporation

Pain Research and Treatment

Volume 2014, Article ID 584986, 9 pages
http://dx.doi.org/10.1155/2014/584986

Research Article
Risk Assessment of Opioid Misuse in Italian Patients with
Chronic Noncancer Pain

Renata Ferrari,1 Genni Duse,2 Michela Capraro,1 and Marco Visentin3

1
Division of Psychology, San Bortolo Hospital, Via Rodolfi, 36100 Vicenza, Italy
2
Pain Management Unit, S. Antonio Hospital, Padua, Italy
3
Pain Management and Palliative Care Unit, San Bortolo Hospital, Vicenza, Italy

Correspondence should be addressed to Renata Ferrari; renata.ferrari@ulssvicenza.it

Received 29 January 2014; Revised 23 June 2014; Accepted 3 July 2014; Published 10 August 2014

Academic Editor: Robert L. Barkin

Copyright © 2014 Renata Ferrari et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective. Opioid therapy in patients with chronic noncancer pain must be preceded by evaluation of the risk of opioid misuse.
The aim of this study was to evaluate the predictive validity of the Italian translation of the Pain Medication Questionnaire (PMQ)
and of the Diagnosis Intractability Risk and Efficacy Score (DIRE) in chronic pain patients. Design. 75 chronic noncancer pain
patients treated with opioids were enrolled and followed longitudinally. Risk of opioid misuse was evaluated through PMQ, DIRE,
and the physician’s clinical evaluation. Pain experience and psychological characteristics were assessed through specific self-report
instruments. At follow-ups, pain intensity, aberrant drug behaviors, and presence of the prescribed opioid and of illegal substances
in urine were also checked. Results. PMQ demonstrated good internal consistency (Cronbach’s 𝛼 = 0.77) and test-retest reliability
(𝑟 = 0.86). Significant correlations were found between higher PMQ scores and the number of aberrant drug behaviors detected at
2-, 4-, and 6-month follow-ups (𝑃 < 0.01). Also the DIRE demonstrated good predictive validity. Conclusions. The results obtained
with specific tools are more reliable than the clinician’s evaluation alone in predicting the risk of opioid misuse; regular monitoring
and psychological intervention will contribute to improving compliance and outcome of long-term opioid use.

1. Introduction terminology is necessary for improving communication and

The problem of poorly controlled pain is still considerable:
in Europe 19% of adults suffer from continuous pain that
seriously compromises the quality of their emotional, social,
and working life [1]. Opioids represent an important option
for pain management; while there is agreement on their
use in acute and cancer pain, long-term use for noncancer
chronic pain remains controversial [2]. Indeed, some patients
benefit from such treatment in terms of pain reduction and
improvement in quality of life, while others do not [3]. Side
effects, absence of any improvement in physical function,
misuse, abuse, and addiction are relatively common dur-
ing chronic opioid administration. The American literature
reports overall rates of opioid misuse and abuse ranging from
4% to 26% [4, 5]. Such different rates may be due to a lack of
a universally accepted definition of terms that describe the
various types of incorrect behavior consequent to chronic
opioid prescription. It is obvious that a clear and accepted
statistics.
In this paper we use the terms misuse and abuse according
to the following definitions [6]. Substance misuse is the use
of any drug in a manner other than how it is indicated or
prescribed, while substance abuse is defined as the use of any
substance when such use is unlawful or when it is detrimental
to the user or to others.
Moreover, the prevalence may depend also on the dif-
ferent populations tested. In Italy there are no data about
opioid misuse and abuse since, until recently, opioids were
not prescribed but in a small percentage of terminal patients
[1, 7], due to regulatory and cultural barriers. In clinical
practice we often find that patients tend to avoid the use of
opioids even if prescribed by specialists; as a consequence,
the health authorities have expressed very little concern about
this problem until now.
Risk factors for opioid abuse and addiction can be
divided into three categories: genetic, substance-related, and
2 Pain Research and Treatment
psychosocial factors. Patients with a personal or family his-
tory of substance abuse and with one or more psychosocial
issues (such as anxiety, depression, personality disorders, or
childhood abuse) are at greater risk of developing addiction,
especially if the treatment is not carefully structured [3].
The aim of pain treatment is effective pain relief and the
consequent functional improvement. Therefore, specialists
are concerned about the possibility of abuse as well as about
the lack of compliance with the analgesic treatment, including
the patient’s decision to decrease the prescribed dosage or to
stop the treatment. For this reason, the detection of aberrant
drug-related behaviors seems to be mandatory. An aberrant
drug-related behavior is defined [8] as any medication-
related behaviors that depart from strict adherence to the pre-
scribed therapeutic plan of care. In line with this definition,
an aberrant behavior is not only an abuse behavior, but also
any behaviors not in accordance with the therapeutic plan or
that may hinder it.
Guidelines recommend that the use of opioids in patients
with chronic noncancer pain must be preceded by an assess-
ment of potential benefits and risks of aberrant drug-related
behaviors and should include a psychological and psychiatric
assessment [2, 9].
In recent years, many tools have been developed for this
purpose [10, 11]: among them, the Pain Medication Ques-
tionnaire (PMQ) [12] and the Diagnosis Intractability Risk
and Efficacy (DIRE) Score [13] were created specifically for
chronic pain patients. The PMQ is a self-report screening
instrument that can easily be integrated into clinical-care
routine. In the original version reliability coefficients were
acceptable, and higher PMQ scores were found to be corre-
lated with a high risk of opioid misuse. In a further study,
significant differences in the mean PMQ score were found
in patients with a history of substance abuse compared with
patients without such a history; moreover, higher PMQ scores
were found in patients who interrupted opioid treatment [14].
The DIRE is an assessment tool used in a multidisciplinary
setting that requires a medical and psychological assessment
of the patient. The psychometric analysis of the original
version of the DIRE showed good internal consistency and
significant correlations between DIRE score and measures of
compliance and efficacy of long-term opioid therapy.
The present study examines the psychometric properties
and clinical utility of the Italian translation of the PMQ
and the DIRE. The predicting validity of the two tools was
assessed by (a) the numbers of aberrant drug behaviors at 2-
, 4-, and 6-month follow-ups and (b) the positivity of urine
toxicology screening performed at 2- and 6-month follow-
ups.
The scores obtained with the two instruments were also
compared with the clinical evaluation made by the physicians
in the pretreatment phase based on their subjective impres-
sion.
Furthermore, as psychosocial distress has been previously
found to be a relevant risk factor in the development of
opioid misuse [3, 12], the relationship between high/low-
PMQ and DIRE scores and measures of anxiety, depression,
and personality traits was also investigated.
2. Materials and Methods
2.1. Subjects. 88 consecutive patients meeting the inclusion
criteria were referred to the Pain Management Units of San
Bortolo Hospital in Vicenza and Sant’Antonio Hospital in
Padua, between December 2009 and January 2012. Inclusion
criteria were age between 18 and 70, presence of noncancer
pain for at least 6 months, a score of 4 or over in the last month
average pain intensity as assessed on an 11-point Numeri-
cal Rating Scale, good knowledge/understanding of Italian,
absence of cognitive deficit, pain not controlled by weak
opioids or other pharmacological and nonpharmacological
treatments used for at least 3 months, and informed consent
to participate in the study. Of these, 75 agreed to participate
in the study (11 refused to participate in the study, while 2
patients were excluded for not filling out the questionnaires
properly); the sociodemographic and clinical characteristics
of the group of subjects are represented in Table 1.
2.2. Instruments. The Pain Medication Questionnaire (PMQ)
[12] is a self-administered questionnaire that describes a ser-
ies of dysfunctional behaviors and characteristics in patients
using analgesics. The tool consists of 26 items, for each of
which the subject must indicate their degree of agreement
on a 5-point Likert scale. A total score is obtained by adding
the scores of the single items. High scores are correlated with
a high risk of opioid misuse. In particular, scores of 25 or
over are predictive of opioid misuse, while scores of 30 or
over suggest that the patient should be frequently monitored
during treatment [15].
The Diagnosis Intractability Risk and Efficacy (DIRE)
Score [13] is a tool that consists of 4 factors: diagnosis, intrac-
tability, risk, and efficacy. Each factor requires assessment on
a 3-point scale, where a score of 1 corresponds to charac-
teristics and behaviors indicative of a negative prognosis
and a score of 3 is indicative of suitability for treatment
with opioids. The risk factor comprises four subcategories:
psychological health, chemical health, reliability, and social
support. The total score can vary from a minimum of 7 to a
maximum of 21; higher scores (≥14) are predictive of good
patient compliance and treatment efficacy.
The medical risk evaluation requires the physician to
provide a clinical estimate based on subjective impression, of
the risk of opioid misuse answering 4 questions on an 11-point
numerical scale: (a) compliance with medical treatment (0 =
no compliance; 10 = maximum compliance), (b) risk of abuse,
(c) risk of underuse of the drug (0 = no risk, 10 = maximum
risk), and (d) expected efficacy of treatment (0 = no efficacy,
10 = maximum efficacy).
The aberrant drug behaviors (ADB): based on the cur-
rent literature [8], a list of 20 aberrant drug behaviors—
that indicate a broad array of problematic nonadherence
behaviors—was created. The physician must tick those behav-
iors displayed by the patient at 2-4- and 6-month follow-ups;
examples of such behaviors are “the patient uses other opioids
in addition to those prescribed” and “the patient displays little
interest in managing himself and his rehabilitation.”
Urine toxicology screening was performed with fast immu-
nodosages that could be read visually, allowing the qualitative
Pain Research and Treatment 3

Table 1: Patients characteristics: demographic, clinical, and psychological variables in the total group and for high and low risk in PMQ and
DIRE.
PMQ scoring group DIRE scoring group
Variables Total sample 𝑁 = 75 𝑃 value1 𝑃 value2
L-PMQa H-PMQb Suit-DIREc NotSuit-DIREd
Age (years)
Mean (SD) 51.5 (11.7) 52.7 (10.8) 53.6 (12.5) — 52.1 (11.3) 50.3 (12.1) —
Gender 𝑁 (%)
Female 57 (76) 34 (82.9) 13 (72.2) — 50 (78.1) 7 (63.6) —
Male 18 (24) 7 (17.1) 5 (27.8) — 14 (21.9) 4 (27.3) —
Marital status 𝑁 (%)
Married 56 (74.6) 33 (80.5) 15 (83.3) — 47 (73.4) 9 (81.8) —
Single 11 (15.3) 5 (12.2) 2 (11.1) — 9 (14.1) 2 (18.2) —
Separated/divorced 7 (9.3) 3 (7.3) 1 (5.6) — 7 (10.9) 0 (0) —
Widowed 1 (1.3) 0 (0.0) 0 (0.0) — 1 (1.6) 0 (0) —
Education (years) 𝑁 (%)
5 9 (12) 6 (14.6) 3 (16.7) — 8 (12.5) 1 (9.1) —
8 26 (34.6) 14 (34.2) 7 (38.9) — 22 (34.4) 4 (36.4) —
8–13 36 (48) 19 (46.3) 7 (38.9) — 31 (48.4) 5 (45.4) —
>13 4 (5.4) 2 (4.9) 1 (5.6) — 3 (4.7) 1 (9.1) —
Employment status 𝑁 (%)
Employed 28 (37.3) 16 (39.0) 6 (33.3) — 24 (37.5) 4 (36.4) —
Unemployed 2 (2.7) 0 (0.0) 2 (11.1) — 2 (3.1) 0 (0) —
Housewife 22 (29.3) 13 (31.7) 5 (27.8) — 17 (26.6) 5 (45.4) —
Retired 23 (30.7) 12 (29.3) 5 (27.8) — 21 (32.8) 2 (18.2) —
Type of pain 𝑁 (%)
Nociceptive 43 (57.3) 22 (53.6) 10 (55.6) — 36 (56.2) 7 (631.6) —
Neurophatic 9 (12) 7 (17.1) 2 (11.1) — 9 (14.1) 1 (9.1) —
Mixed 23 (30.7) 12 (29.3) 6 (33.3) — 19 (29.7) 3 (27.3) —
Duration of pain (months)
Mean (SD) 125.9 (105.9) 138.9 (107.7) 106.3 (93.7) — 128.4 (99.1) 118.7 (121.0) —
Psychological variables
STAI Y2
Mean (SD) 50.6 (9.3) 46.7 (6.9) 56.5 (10.4) <0.01 49.6 (8.4) 55.9 (11.9) <0.05
BDI-2 total
Mean (SD) 21 (10.7) 16.5 (8.6) 28.0 (11.5) <0.01 19.2 (9.2) 30.5 (13.6) <0.05
PRSS catastrophe
Mean (SD) 3.0 (1.1) 2.6 (1.1) 3.8 (0.7) <0.01 2.9 (1.1) 3.6 (0.9) —
MMPI hypochondriasis∗
Mean (SD) 17.2 (5.2) 15.3 (3.9) 20.2 (4.7) <0.01 16.9 (5.5) 19.1 (4.4) —
MMPI depression∗
Mean (SD) 29.8 (5.4) 28.2 (4.7) 32.0 (6.1) <0.01 29.2 (5.1) 32.7 (6.0) —
MMPI hysteria∗
Mean (SD) 31.6 (4.8) 30.4 (4.4) 32.9 (4.8) — 19.6 (5.1) 32.7 (6.0) —
MMPI psychopathic D∗
Mean (SD)∗ 20.3 (5.3) 18.7 (5.1) 23.3 (4.8) <0.01 19.6 (5.1) 24.0 (4.6) —
MMPI-mascul./feminin.∗
Mean (SD)∗ 31.4 (4.6) 30.3 (4.2) 31.7 (4.5) — 30.5 (4.1) 31.6 (4.0) —
MMPI Paranoia∗
Mean (SD) 11.8 (3.4) 10.3 (2.2) 14.3 (2.7) <0.01 11.2 (3.0) 14.8 (3.9) —
4 Pain Research and Treatment
Table 1: Continued.
PMQ scoring group
Variables Total sample 𝑁 = 75
L-PMQa
MMPI psychasthenia∗
Mean (SD) 20.7 (8.3) 18.1 (8.6)
∗
MMPI Schizophrenia
Mean (SD) 20.8 (10.4) 17.3 (9.7)
MMPI Hypomania∗
Mean (SD) 18.5 (4.3) 17.8 (4.4)
MMPI social introver.∗
Mean (SD) 32.6 (7.2) 32.6 (6.3)
a b
L-PMQ group, 𝑛 = 41 (PMQ total score <25); H-PMQ group, 𝑛 = 18 (PMQ total score ≥30).
c
Suitable-DIRE group, 𝑛 = 64 (DIRE total score ≥14). d Not suitable-DIRE group, 𝑛 = 11 (DIRE total score ≤13).
∗
Row total scores (no 𝐾-correction).
𝑃 value: significant differences in mean scores between PMQ scoring groups (𝑃 value1 ) and between DIRE scoring groups (𝑃 value2 ).
determination of the pharmacological substances and their
metabolites present in the urine. For opiates, marijuana, and
buprenorphine, QuikStrip OneStep immunodosages by Syn-
tron Bioresearch were used; QuikPac IITM OneStep was used
to detect the presence of amphetamines, methamphetamines,
cocaine, and oxycodone. In case of uncertainty the urine
sample was sent to the laboratory for gas chromatography
confirmation.
The psychological assessment included a structured inter-
view and the following tools.
The Visual Analogue Scale (VAS) consists of a 10 cm long
horizontal line, the start and end points of which are labeled
“no pain” and “worst possible pain,” respectively. The patient
is asked to mark the points corresponding to his/her worst,
least, and average pain intensity in the last month.
The Minnesota Multiphasic Personality Inventory II
(MMPI-2) [16, 17] is a 567-true-false-item self-report ques-
tionnaire which assesses psychiatric symptoms and person-
ality organization; after checking for validity indicators (in
order to screen out invalid protocols) only the ten basic
clinical scales were used to indicate different psychological
conditions.
The Beck Depression Inventory II (BDI-II) [18, 19] is a 21-
item self-administered questionnaire used to determine the
patient’s depressive reaction, assessing both the cognitive and
the somatic components.
The State Trait Anxiety Inventory-Y (STAI-Y) [20, 21] is a
40-item questionnaire that assesses the level of patient anx-
iety; two scores can be obtained referring to state and trait
anxiety.
Finally, the Pain Related Self-Statement Scale (PRSS)
[22, 23] is a self-administered scale developed to assess the
cognitions specifically triggered in pain situations that might
inhibit or promote coping responses. Two total scores can be
obtained for the subscales catastrophizing and coping.
2.3. Procedure. This is an observational, prospective, and lon-
gitudinal study, and it consisted of the following assessment
phases: patient selection, collection of pretreatment data,
DIRE scoring group
𝑃 value1 𝑃 value2
H-PMQb Suit-DIREc NotSuit-DIREd
23.8 (7.1) <0.01 19.1 (7.8) 27.0 (7.8) —
25.8 (10.5) <0.01 18.8 (9.7) 29.5 (9.6) <0.01
19.4 (4.2) — 18.5 (4.3) 18.6 (3.2) —
33.5 (8.7) — 31.3 (6.3) 39.5 (7.6) —
and 2-, 4-, and 6-month follow-ups. The specialist physician
selected patients according to the clinical criteria indicated
above. Pretreatment data were collected in the two-week
period following selection. It included the filling-out of the
PMQ by the patient and of the DIRE by the multidisciplinary
team. Questionnaires to assess the pain intensity (VAS), cop-
ing strategies (PRSS), affective/emotional condition (STAI-
Y, BDI-II), and personality characteristics (MMPI-2) were
also administered in pretreatment assessment. Medical and
psychological follow-ups were scheduled 2, 4, and 6 months
after the start of treatment and included the filling-out of
ADB and the readministration of VAS, STAI, and BDI-II. At
each follow-up session patients were also required to collect
a urine specimen which was immediately examined by the
same person in both centers; in case of uncertainty the urine
sample was sent to the laboratory for gas chromatography
confirmation.
Both PMQ and DIRE were translated by the authors,
according to the guidelines for the process of cross-cultural
adaptation of self-report measures, and approved by the first
author of each instrument.
The study protocol was approved by the Institutional
Ethic Committee of both hospitals.
2.4. Statistical Analysis. Continuous variables are expressed
with mean, standard deviation, minimum and maximum,
and centiles, when appropriate. As the studied variables
were not normally distributed (assessed by Kolmogorov-
Smirnov test), to examine the differences between continuous
variables, Kruskal-Wallis and Kolmogorov-Smirnov non-
parametric analyses of variance tests were used; Chi-square
test was used for the comparison of frequency distributions.
Repeated measures ANOVA was used to analyze the presence
of significant differences in pain intensity among patients at
high/low risk of opioid misuse. Bonferroni correction was
used in post hoc analysis to control for type II errors. The
reliability was assessed through test-retest Pearson’s 𝑟 (PMQ)
and internal consistency was determined by Cronbach’s
𝛼 (PMQ and DIRE). Spearman’s nonparametric coefficient
Pain Research and Treatment 5

was used to examine the relationship between the PMQ and 100
DIRE scores and the number of aberrant drug behaviours 90
detected at the medical follow-up.

Pain intensity (VAS)

80
70
3. Results and Discussion
60
3.1. Results. All patients reported continuous pain; Figure 1 50
shows the mean values of worst, least, and average pain
40
intensity in the four assessment phases. The most frequently
administered analgesic was oral oxycodone (50.7%), followed 30
by fentanyl (40%). No significant age and gender differences 20
were found at baseline in worst, least, and average pain Baseline 2 4 6
intensity. Months of follow-up
In the repeated measures ANOVA, both worst and aver- Worst
age pain as measured with VAS underwent a statistically Average
significant (𝑃 < 0.001) reduction at 2-, 4-, and 6-month Least
follow-ups; no statistically significant changes in VAS scores
from baseline to 6-month follow-up were related to age, sex, Figure 1: Pain intensity in the VAS scales before opioids and in
and type of pain. The adherence to the treatment protocol was subsequent 2-, 4-, and 6-month follow-ups.
very high; only four out of 75 patients dropped the treatment
due to side effects.
Approximately one-third of the patients (35%) reported
𝑃 < 0.001). As for the predictive validity of the tool, highly
the presence of at least one side effect at follow-up; the most
sig-nificant correlations were found between the total PMQ
frequently reported side effects were sleepiness (12%), nausea
score and the number of aberrant drug-related behaviors at
(11.3%%), and constipation (8.8%).
2-month (𝑟 = 0.58; 𝑃 < 0.01), 4-month (𝑟 = 0.67; 𝑃 < 0.01),
At 6-month follow-up, 46.2% of patients did not display
and 6-month follow-ups (𝑟 = 0.52; 𝑃 < 0.01). The mean
any aberrant drug-related behaviors, 15.4% manifested only
time required by the patient to complete the questionnaire
one, and the remaining 38.4% manifested two or more.
was 12󸀠 16󸀠󸀠 (SD = 5.23; range: 4–30).
In particular, 28.2% showed little interest in managing
According to the cut-offs established by Dowling et al.
themselves and in rehabilitation, 24% frequently cancelled
[15], 41 subjects (54.7%) were at low risk, 16 (21.3%) at
appointments, and 12.6% reported minimal or inadequate
moderate risk, and 18 (24%) at high risk of drug misuse. The
pain relief.
distribution in the three risk levels between men and women
The urine toxicology screens with immunoassay did not
was comparable.
identify the prescribed opioid in only one patient at the two-
Nonparametric analysis of variance confirmed the pres-
month follow-up, whereas it was identified in all patients at
ence of a significantly higher number of aberrant drug-related
the 4- and 6-month follow-ups. In only one patient the result
behaviors in the high-PMQ group compared to the low-PMQ
was questionable for illegal substances (suspect positivity for
group detected at 2-month (𝑍 = 2.16; 𝑃 < 0.001), 4-month
cocaine): so gas chromatography determination was made,
(𝑍 = 2.64; 𝑃 < 0.001), and 6-month follow-ups (𝑍 =
which resulted negative.
2.38; 𝑃 < 0.001) (Figure 2).
As regards the psychological variables investigated in the
One-way repeated measures ANOVA showed a minor
pretreatment assessment (mean scores in Table 1) we found
reduction in the worst pain intensity in the high-PMQ and
that, based on the personality profile obtained with MMPI-2,
moderate-PMQ groups when compared to the low-PMQ
24.5% of women and 27.7% of men had clinically significant
group (𝐹1,70 = 6.75; 𝑃 < 0.01) (Figure 3).
scores (𝑇 scores ≥ 65) in at least one of the clinical scales
The group was subsequently divided, according to the
with psychopathological content (Paranoia, Schizophrenia,
scores obtained at PMQ, in order to analyze the presence
and Hypomania). As for the affective-emotional variables, the
of any significant differences in the psychological variables
depression score at BDI-2 was clinically significant (scores
considered in the study.
higher than 95th percentile) in 52.2% of patients; at STAI-trait
In general, Kruskal-Wallis analyses revealed significant
anxiety 22.5% of patients showed a clinically significant score
differences (𝑃 < 0.01) between high- and low-PMQ scores
of anxiety.
in the following clinical scales: STAI-trait anxiety, BDI-total
score, PRSS catastrophizing, MMPI hypochondriasis, MMPI
3.1.1. Analysis of the PMQ. The sample (𝑁 = 75) yielded a depression, MMPI psychopathic deviate, MMPI Paranoia,
mean PMQ score of 25.4 (±10.35), a median score of 24, and MMPI psychasthenia, and MMPI Schizophrenia. As it can
a mode of 20 (lowest score = 8; highest score = 62). There were be seen in Table 1, the high-PMQ group showed significantly
no significant age and gender differences in the PMQ scores. higher mean scores than the low-PMQ group in all these
Analysis of internal consistency produced an alpha coef- clinical scales. Moreover, 26% of patients with high PMQ and
ficient of 0.77, indicating an adequate internal coherence; the 12.3% of those with low PMQ obtained clinically significant
test-retest reliability at 2 months was very high (𝑟 = 0.86; scores (𝑇 scores ≥ 65) in at least one of the MMPI-2 clinical
6 Pain Research and Treatment

2.5 Pain intensity and DIRE scoring groups

100

Mean scores worst VAS

95

1.5 90
ADB

85
1

80
0.5
75
Baseline 2 4 6
0 Months of follow-up
2 4 6
Suitable
Months of follow-up
Not suitable
L-PMQ Suit-DIRE
H-PMQ Not suit-DIRE Figure 4: Mean scores of worst pain intensity (VAS) in the
pretreatment phase and at 2-, 4-, and 6-month follow-ups relative
Figure 2: Mean frequency of aberrant drug-related behaviors to suitable (total score ≥14) and not suitable (total score ≤13) DIRE
(ADB) for high risk (H-PMQ) and low risk (L-PMQ) of drug misuse scoring groups.
at PMQ and for low risk (Suit-DIRE) and high risk (Not suit-DIRE)
at DIRE.
candidates to start chronic opioid treatment according to
the cut-offs established by Belgrade et al. [13]. No significant
Pain intensity and PMQ scoring groups age and gender differences were found in the distribution
of the two risk levels. The internal consistency of the Italian
100 translation of the tool was 0.39, which is very low; the item
95 that contributed least to the internal consistency of the DIRE
Mean scores worst VAS

was diagnosis (𝛼 if item deleted = 0.48).

90 In Figure 2 the mean frequencies of aberrant drug-related
85 behaviors at follow-up for “suitable” and “not suitable” DIRE
scores are shown, with significantly higher numbers of those
80 behaviors in the “not suitable” group (𝑃 < 0.01) in all
75 the assessment times. With regard to the predictive validity
of the tool, significant correlations were found between a
70 lower total DIRE score (higher risk of opioid misuse) and a
Pretreatment Months of follow up higher number of aberrant drug-related behaviors detected at
2-month (𝑟 = −0.37; 𝑃 < 0.01), 4-month (𝑟 = −0.35; 𝑃 <
Low risk 0.01), and 6-month follow-ups (𝑟 = −0.34; 𝑃 < 0.01).
Moderate risk Besides, “suitable” for opioid therapy patients showed a
High risk greater reduction in the worst pain intensity (VAS = 78.8; SD
Figure 3: Mean scores of worst pain intensity (VAS) in the = 16.3) than “not suitable” patients (VAS = 87.3; SD = 11.3)
pretreatment phase and at 2-, 4-, and 6-month follow-ups relative (𝐹1,70 = 5; 𝑃 < 0.05) at 6-month follow-up (Figure 4).
to low (scores < 25), moderate (<25–29>), and high (>30) PMQ In order to investigate the presence of any significant
scoring groups. differences in psychological variables, “suitable for opioid
therapy” patients, based on DIRE score, were compared to
“not suitable” for therapy patients.
Kolmogorov-Smirnov analysis underlined the presence
scales with psychopathological content (Paranoia, Schizo- of significantly higher mean scores (𝑃 < 0.01) in the “not
phrenia, and Hypomania). suitable” group on two MMPI-2 scales: frequency (𝑍 = 1.81)
and Schizophrenia (𝑍 = 1.66); a tendency toward significant
3.1.2. Analysis of the DIRE. In the DIRE, the scores varied differences (𝑃 < 0.05) was even found on STAI-trait anxiety
from 12 to 19, with a mean of 15.7 (SD = 1.8) and both med- (𝑍 = 1.37) and BDI-total score (𝑍 = 1.39) scales, with lower
ian and mode of 16; there were no significant differences scores in the “suitable” for opioid therapy group (Table 1).
between the mean scores of men (14.8; SD = 1.5) and women The mean time required by the multidisciplinary team to
(15.9; SD = 1.7). 85.3% of patients were found to be good complete the tool was 7󸀠 37󸀠󸀠 (SD = 3.21; range: 1–16).
Pain Research and Treatment
3.1.3. PMQ, DIRE, and the Medical Risk Evaluation. As for the
concurrent validity of the PMQ and DIRE, a significant
negative correlation (𝑟 = −0.40; 𝑃 < 0.01) between high total
PMQ scores (high risk of opioid misuse) and low DIRE total
scores (not suitable) was found. As regards the 4 subscales of
the medical risk evaluation, positive correlations (𝑃 < 0.01)
were only found between the physician’s estimate of the
“opioid abuse” subscale and aberrant drug-related behaviors
at 2-month (𝑟 = 0.32) and 6-month follow-ups (𝑟 = 0.39). No
significant correlations emerged between the four scales of
the medical risk evaluation and the PMQ total score. Instead,
significant positive correlations (𝑃 < 0.01) were found
between DIRE total score and the physician’s evaluation of
“compliance to treatment” (𝑟 = 0.33) and “treatment efficacy”
(𝑟 = 0.34) while the DIRE total score correlates negatively
with the physician’s estimate of “opioid abuse” (𝑟 = −0.35)
and risk of “underuse” (𝑟 = −0.34).
3.2. Discussion. The main aim of this study was to evaluate
the preliminary validity of the Italian translation of the
Pain Medication Questionnaire (PMQ) and the Diagnosis
Intractability Risk and Efficacy Score (DIRE) in predicting
the risk of opioid misuse in patients with chronic noncancer
pain.
The total group of 75 patients had a mean age of 51.5
years, with a prevalence of females (76%), and a long history
(roughly 10.5 years) of severe chronic pain condition, most
often classified as nociceptive.
As for the psychological variables considered in the study,
half of the samples reported clinically significant levels of
depression and 22.5% of the patients displayed high levels of
anxiety. In addition, there was a high incidence of elevation
in patients’ personality profiles: 24.5% of women and 27.7% of
men reported clinically significantly high scores in at least one
of the clinical content scales of the MMPI-2. These data are
in line with the findings of many authors [24–26] and suggest
the need to involve a psychotherapist in the assessment and
treatment process of this population [9, 27].
According to the PMQ scores, about half of the group
(53.3%) showed no particular risks of opioid misuse, while
24% of the subjects were found to be at high risk. A strong
correlation was found between high-PMQ scores and the
number of aberrant drug behaviors after 2, 4, and 6 months
of treatment. No significant differences in demographic vari-
ables emerged between high- and low-PMQ scoring groups.
A further interesting result is represented by the lower
pain reduction that occurred in patients at high risk of
misuse, possibly due to inadequate use of the prescribed
opioids. Patients classified as high risk of misuse, based on
the cut-offs suggested by Dowling et al. [15], were found to be
significantly more anxious and depressed and had a greater
tendency to focus on physical symptoms and worry about
them.
High-risk patients also reported higher mean scores and
a higher percentage of clinically significant scores on the
“Paranoia,” “Schizophrenia,” and “Hypomania” scales of the
MMPI-2. Thus, the elevation of these scales, characterized
by psychopathological traits, as well as a passive attitude in
7
managing pain condition, and a greater tendency to produce
pessimistic and catastrophic thoughts about pain are asso-
ciated with a higher risk of opioid misuse. The association
of high-PMQ scores, symptoms of depression, and psycho-
logical distress appears to be in line with previous findings
[12, 28]. Furthermore, the PMQ has demonstrated adequate
internal consistency and good reliability over the time. In
addition, the short time required to complete the PMQ makes
it easy to integrate it into clinical routine.
All these data suggest that the tool provides a reliable
estimate of the risk of medication misuse and appears to be
a reliable indicator that the clinician can use to plan regular
treatment monitoring. The strong association of high-PMQ
scores and the presence of symptoms of depression, anxiety,
hypochondria, and catastrophizing suggest that opioid ther-
apy needs to be combined with psychological treatments to
reduce the affective and emotional distress and modify the
patient’s dysfunctional beliefs and behaviors related to the use
of these drugs.
Also for the Italian translation of the DIRE, the results
show that the total score is a good predictor of the risk
of drug misuse: patients that obtained low scores in this
instrument showed a significant greater frequency of aberrant
drug-related behaviors in all the assessment times than those
classified as good candidates for opioid therapy. Besides,
suitable patients obtained a greater improvement in pain
control than poor candidates at 6-month follow-up.
However, the DIRE has low internal consistency: this
means that the items are very heterogeneous and that the
tool probably has a multifactorial structure. Thus, our finding
does not agree with the results reported by Belgrade et al. [13]
in the original validation study, in which the DIRE displayed
an internal consistency of 0.80.
Poor candidates for opioid treatment according to the
DIRE score reported higher mean scores in anxiety, depres-
sion, and Schizophrenia-MMPI scales when compared to the
good candidates. These results are consistent with previous
findings, which identified the presence of psychiatric disor-
ders as one of the most predictive factors of opioid abuse [29,
30]. Completing the DIRE requires a few minutes, but it must
be preceded by a multidimensional and interdisciplinary
assessment of the patient.
The two tools selected appear to be correlated; then both
assess the same construct.
The physician’s risk evaluation was found to be valid in
estimating only the risk of opioid abuse at 2- and 6-month
follow-ups; there were no significant relations between aber-
rant drug behaviors and medical risk evaluation of com-
pliance with treatment, underuse of the drugs, or efficacy
of treatment. Moreover, the correlations found between the
physician’s subjective evaluation for the risk of opioid abuse
and the number of aberrant drug behaviors were weaker
when compared to those obtained by using the PMQ and
the DIRE. This result highlights the need to integrate clinical
evaluation with the use of tools specifically created to assess
the risk of opioid misuse in the chronic pain patient.
The urine toxicology screens were not able to identify the
prescribed opioids only in one specimen out of 71. On the
other hand, no illegal drugs were identified in any specimen.
8 Pain Research and Treatment
These data seem rather surprising compared with those
reported by other authors in USA studies, who found up to
46.5% of the sample to have abnormal urine toxicology screen
results [31–34].
The preliminary results seem to suggest that in our con-
text the most frequent problem may be the underuse of
opioid analgesics rather than their compulsive use and abuse
as reported in the American literature: this interpretation
is supported by the difficulty, frequently expressed by our
patients and their families, in accepting these drugs for fear
of addiction, loss of mental lucidity, or social stigmatization.
This attitude seems to reflect the history of limited opioid
use in Italy, which is one of the countries with the lowest
morphine consumption in Europe [1, 7].
A further important objective of the multidisciplinary
team is thus to assess patients’ beliefs about these drugs so as
to be able to modify any dysfunctional and unrealistic expec-
tations. At the same time, the use of tools that allow identify-
ing patients at risk of opioid misuse can reassure physicians
that often tend to overestimate the risk of addiction. The
short time required by the patient and the multidisciplinary
team to complete their respective questionnaires supports the
routinely use of these instruments in the clinical setting.
One may object that if universal precautions are used,
stratification seems irrelevant. In fact this study reflects the
Italian situation, where the Government has recently issued
regulations aiming at promoting the use of analgesic opioids
for therapeutic purposes. Consequently, we can expect the
number of patients treated with opioids to grow significantly
in the next years. The majority of these patients will be
cared for by the General Practitioners who may not have
the experience in the field or the time necessary to follow
all of them with the maximal diligence according to the
universal precautions. Hence it is important to carry out
stratification of the risk of drug misuse before starting chronic
opioid treatment, so that high-risk patients can be referred
to interdisciplinary pain relief centers where they can be
carefully monitored and trained on self-reliance.
In contrast with what is reported in the literature [31, 34],
the adherence to the treatment protocol was very high; a
possible explanation is that patients in our cohort had a long
history of pain and they were probably highly motivated in
the treatment prescribed by a specialized pain relief center.
Besides, the frequent and scrupulous follow-up sessions that
allowed rapid treatment and prevention of possible adverse
events could have encouraged our subjects to maintain the
therapy.
4. Conclusions
Our results support the adequate psychometric properties
and clinical utility of the two screening measures employed.
Besides, both PMQ and DIRE are more reliable than the clini-
cian’s evaluation alone in predicting the risk of opioid misuse,
and the brevity in the administration allows their routinely
use in a clinical setting. Both tests appear to be predictive
of patient compliance and efficacy of analgesia in long-term
opioid analgesic treatment. Nevertheless, the PMQ brevity of
administration made it more useful for screening purposes
in primary care setting, where the assessment is made in a
short time and by General Practitioners. On the other hand,
the DIRE required a multidisciplinary assessment, including
an in-depth examination of psychosocial characteristics and
attitude towards drugs and therapy. For this reason it could
be more easily conducted in an interdisciplinary pain relief
center to identify the specific support needs of the patient.
The limitations of this study are primarily the small
number of subjects enrolled and the differing distribution
of men and women. Despite these limitations, the study
has allowed us to conduct preliminary analyses on the
predictive validity and psychometric properties of the Italian
translation of the PMQ and the DIRE, as well as to analyze
affective-emotional variables and personality characteristics
in patients treated with opioids.
Overall, our results highlight the need for a multidisci-
plinary assessment of patient candidates for chronic opioid
treatment and for the use of tools specifically designed to
predict the risk of misuse. Regular monitoring, psychological
interventions, and urine drug screening will contribute to
improve the compliance and outcome of long-term opioid
use.
Conflict of Interests
The authors declare that there is no conflict of interests
regarding the publication of this paper.
Acknowledgments
The study has been carried out without any funding. The
authors would like to express their gratitude to the staff of
the Pain Management Units in S. Bortolo Hospital, Vicenza,
and in S. Antonio Hospital, Padua, for their help with the data
collection.
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